USE OF COMPOUND BINDING TO MSIN3B THAT SPECIFICALLY BINDS TO NEURON RESTRICTIVE SILENCER FACTOR (NRSF)
申请人:Nishimura Yoshifumi
公开号:US20130203738A1
公开(公告)日:2013-08-08
The present invention identifies a compound which binds to the PAH1 domain of mSin3B that specifically binds to neural restrictive silencer factor NRSF, and uses the compound as a prophylactic and/or a therapeutic for diseases associated with abnormal expression of neural restrictive silencer factor NRSF/REST or abnormal expression of genes targeted by NRSF/REST, such as Huntington's disease, medulloblastoma and neuropathic pain.
The present invention provides a pharmaceutical composition comprising a substance capable of binding to the PAH1 domain of mSin3B, e.g., a compound represented by the following formula (I), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof:
wherein n represents 0 or 1; R
1
, R
2
, R
3
, R
4
and R
5
each independently represent a hydrogen atom, a hydrocarbon group or a functional group; Y represents a single bond, a carbonyl group, —CONH—, —NHCO— or a sulfonyl group; and Z represents a nitrogen-containing heterocyclic group which may have a substituent, an amino group which may have a hydrocarbon group or an aromatic hydrocarbon group, or a nitrogen and oxygen-containing heterocyclic group which may have a substituent.
本发明鉴定了一种结合mSin3B的PAH1结构域的化合物,该化合物特异性地结合神经限制性沉默因子NRSF,并将该化合物作为预防和/或治疗与神经限制性沉默因子NRSF/REST异常表达或受NRSF/REST靶向的基因异常表达相关的疾病,如亨廷顿病、髓母细胞瘤和神经病理性疼痛。本发明提供了一种制药组合物,包括能够结合mSin3B的PAH1结构域的物质,例如,由以下式(I)表示的化合物,其药理学上可接受的盐或酯:其中n代表0或1;R1、R2、R3、R4和R5各自独立地表示氢原子、碳氢基团或功能基团;Y表示单键、羰基、—CONH—、—NHCO—或磺酰基;Z表示氮杂环基团,该氮杂环基团可以具有取代基,氨基可以具有碳氢基团或芳香碳氢基团,或者氮和氧杂环基团可以具有取代基。